TLR4 Enhances Cerebral Ischemia/Reperfusion Injury via Regulating NLRP3 Inflammasome and Autophagy.

Ischemic stroke is a kind of central nervous disease characterized by high morbidity, high mortality, and high disability. Inflammation and autophagy play important roles in cerebral ischemia/reperfusion (CI/R) injury. The present study characterizes the effects of TLR4 activation on inflammation and autophagy in CI/R injury. An in vivo CI/R rat injury model and an in vitro hypoxia/reoxygenation (H/R) SH-SY5Y cell model were established. Brain infarction size, neurological function, cell apoptosis, inflammatory mediators' levels, and gene expression were measured. Infarction, neurological dysfunction, and neural cell apoptosis were induced in CI/R rats or in H/R-induced cells. The expression levels of NLRP3, TLR4, LC3, TNF-α, interleukin-1 (IL-1), interleukin-6 (IL-6), and interleukin-18 (IL-18) clearly increased in I/R rats or in H/R-induced cells, while TLR4 knockdown significantly suppressed NLRP3, TLR4, LC3, TNF-α, and interleukin-1/6/18 (IL-1/6/18) in H/R-induced cells, as well as cell apoptosis. These data indicate that TLR4 upregulation induced CI/R injury via stimulating NLRP3 inflammasome and autophagy. Therefore, TLR4, is a potential therapeutic target to improve management of ischemic stroke.

[Situation analysis of outcome indicators of randomized controlled trials of traditional Chinese medicine in treatment of hypertensive intracerebral hemorrhage in recent three years].

The study aims to analyze the outcome indicators of randomized controlled trial(RCT) of traditional Chinese medicine(TCM) in the treatment of hypertensive intracerebral hemorrhage(HICH) in recent three years, and thus provide suggestions for the future studies in this field. Four English databases, four Chinese databases and two online registration websites of clinical trials were searched. The RCTs published between January 2018 and September 2020 were screened. The risk of bias was assessed and outcome measures were classified. A total of 151 839 articles were retrieved, of which 44 RCTs were included for analysis after screening. The outcome measures of the included RCTs were classified into 7 categories, among which the symptoms/signs category showed the highest reporting rate. National Institute of Health stroke scale(72.73%) was the most frequently reported outcome indicator, while the vo-lume of intracerebral hemorrhage determined by computerized tomography(36.36%) was the most frequently reported lab test outcome. Most studies collect the outcomes at the end of treatment, while 9 studies reported long-term outcomes 3 months or more after onset. Compared with those of international clinical trials, the application of some of the outcomes was reasonable, focusing on patients' symptoms, quality of life and objective outcomes. However, there were still several problems: unclear primary and secondary outcome measures, insufficient attention to long-term prognosis, insufficient attention to social function, few TCM outcomes, lack of measurement blindness and the use of unreasonable composite outcomes. It is recommended that researchers should rationally design the outcome indicators of clinical trials and develop the core outcome set.

Capsaicin and dihydrocapsaicin induce apoptosis in human glioma cells via ROS and Ca2+­mediated mitochondrial pathway.

Human glioma is the most common type of primary brain tumor and one of the most invasive and aggressive tumors, which, even with treatments including surgery, radiotherapy and chemotherapy, often relapses and exhibits resistance to conventional treatment methods. Developing novel strategies to control human glioma is, therefore, an important research focus. The present study investigated the mechanism of apoptosis induction in U251 human glioma cells by capsaicin (Cap) and dihydrocapsaicin (DHC), the major pungent ingredients of red chili pepper, using the Cell Counting Kit­8 assay, transmission electron microscopy analysis, flow cytometry analysis, laser scanning confocal microscope analysis and immunohistochemical staining. Treatment of U251 glioma cells with Cap and DHC resulted in a dose­ and time­dependent inhibition of cell viability and induction of apoptosis, whereas few effects were observed on the viability of L929 normal murine fibroblast cells. The apoptosis­inducing effects of Cap and DHC in U251 cells were associated with the generation of reactive oxygen species, increased Ca2+ concentrations, mitochondrial depolarization, release of cytochrome c into the cytosol and activation of caspase­9 and ­3. These effects were further confirmed by observations of the anti­tumor effects of Cap and DHC in vivo in a U251 cell murine tumor xenograft model. These results demonstrate that Cap and DHC are effective inhibitors of in vitro and in vivo survival of human glioma cells, and provide the rationale for further clinical investigation of Cap and DHC as treatments for human glioma.

[Effects of granules for nourishing kidney and strengthening brain on main symptoms of kidney-yin deficiency and blood stasis syndrome and hemorrheological characteristics of brain atrophy].

OBJECTIVE: To explore the influence of granules for nourishing kidney and strengthening brain (GNKSB) on main symptoms of kidney-yin deficiency and blood stasis syndrome and the hemorrheological characteristics of brain atrophy patients. METHODS: Ninety patients of brain atrophy with kidney-yin deficiency and blood stasis syndrome were randomly divided into two groups. Sixty cases in treatment group were treated with GNKSB, and the 30 cases in control group were treated with piracetam for 8 weeks. RESULTS: The effective rate of treatment group was 73.3%, with significant difference as compared with 46.6% of the control group (P<0.01). The scores of symptom-assessment of the two groups were also significantly different (P<0.01). The mini-mental state examination of treatment group was obviously improved, and was significantly different as compared with the control group (P<0.01). The scores of Hasegawa's dementia scale and activities of daily living were increased, but without significant difference as compared with the control group. The platelet aggregation rate was improved, with significant difference as compared with the control group (P<0.05). The whole blood viscosity was also improved obviously, but without significant difference as compared with the control group. CONCLUSION: GNKSB is effective for kidney-yin deficiency and blood stasis syndrome of brain atrophy patients and can improve their mental state and the hemorrheological indexes.